The objectives of this program are to: a. Define the natural history, pathogenesis and pathophysiology of the plasma cell dyscrasias and characterize the monoclonal immunoglobulins associated with PCDs with respect to specific antibody activities and physicochemical properties which relate to specific pathophysiological manifestations in individual cases, e.g., amyloidosis, hyperviscosity, disturbances of lipid metabolism, coagulation defects and renal dysfunction (Project I -Osserman). b. Define the sequence of reactions involved in the assembly of monoclonal immunoglobulins and their binding of haptens (Projectt II - Beychok). c. Screen monoclonal immunoglobulins for anticarbohydrate activity with the goal of identifying specific proteins for detailed analysis of primary, secondary and tertiary structure (Project III - Kabat). d. Define the cellular abnormalities in the plasma cell dyscrasias, i.e., the possible involvement of R as well as B cells and plasma cells, the distribution patterns of specific markers including idiotypic determinants (Project IV - Halper). e. Investigate the specific interactions between the apparently neoplastic clones in the PCDs and the remaining immune system considered as a network of mutually regulating clones (Project IV - Pernis).